Wounds in cornea, sclera and tendons heal slowly and rarely achieve the strength of the unwounded tissue. The relative weakness of corneal and scleral wounds leaves a large number of patients at risk in the event of impact if they have had lens extractions, corneal transplants or radial keratotomy. The tensile strength of dense connective tissue is usually due to collagen fibrils so it may be deduced that either the structure or organization of the wound collagen or its interaction with the surrounding connective tissue is deficient. Drugs, growth factors and surgical techniques all can affect the rate of healing and the strength of the scar, and the ultimate strength may change with progressive remodeling. We will study the ultratructure of healing wounds in collagenous tissue and the variables that limit and control the strength of the wound. We have recently explored the feasibility of covalently labeling in vivo connective tissue with dyes and other reagents that can be detected in light and electron microscope sections. We propose to apply these reagents to rabbit corneas, sclera and tendons and then after making an incision we will examine the organization of the labeled (original) collagen and the newly synthesized collagen at intervals as remodeling occurs. These studies will be made at the light and electron microscope level with avidin-peroxidase and autoradiography with tritium and [125l] tracers. We will correlate the effects of different surgical procedures and drugs on the tensile strength of the tissue, the collagen organization in the scar, the collagen types and their crosslinking. In collaboration with Dr. C. Puliafito (Mass. Eye and Ear Inf.) studies will be extended to compare healing incisions made in the cornea and sclera by the excimer laser. The techniques developed for these investigations will in the future find application in analyzing connective tissue changes that are formative in the stages of animal development and may be useful in examing the growth processes occurring in ectasias such as keratoconus.